DESCRIPTION: (Applicant's Abstract) Glaucoma is a term used to describe a group of disorders which have in common a characteristic degeneration of the optic nerve usually associated with elevated intraocular pressure. Glaucoma is the third most prevalent cause of visual impairment and blindness among white Americans and is the leading cause of blindness among black Americans. Despite many decades of research, little is known about the cause of this disease on a molecular level. An obstruction to the outflow of aqueous humor through the trabecular meshwork is probably a major cause of the increase in intraocular pressure in open angle glaucoma, but the processes that lead to this obstruction have not been determined. A number of different studies provide compelling evidence indicating that the susceptibility to primary open-angle glaucoma is inherited. The complexity of the genetic nature of this disorder requires a large broad-based collaborative effort to adequately address the inheritance of this disease. We propose to collect pedigrees affected with primary open angle glaucoma and use these families to identify regions of the human genome which may harbor loci responsible for this disorder. Using uniform and strict clinical criterion, pedigrees affected with primary open angle glaucoma will be collected from two separate geographic regions. The pedigrees collected from each site will be used to create two independent but comparable data sets. Initially different parts of the genome will be screened by each site using the pedigrees collected at that site. Microsatellite repeat markers located at 10 cM intervals throughout the genome will be used for genotype generation. Data from the genotype screen will be used to create data-bases for linkage analysis at each site. Potential areas suggestive of linkage detected at one site will be confirmed by the data-set from the second site before initiating comprehensive molecular studies of the region. Additional follow up studies to investigate the clinical and genetic heterogeneity of this disease will also be facilitated and confirmed by an available second data-set. This collaborative approach using independent but similar data-sets will be an extremely efficient and effective method to identify regions of the human genome containing genes responsible for this important blinding disease.